The long term objectives of this new K08 application are to develop the applicant's expertise to conduct independent and creative research in an area of oral biomedical sciences that is relevant to the specialty of Oral Pathology. Support for five years, including three years of formal research training towards a Ph.D. degree is requested. The candidate was a former oral pathology resident at the Baylor College of Dentistry and will expand upon her scientific skills through a unique integration of interdepartmental resources. The career development plan proposes a phased and integrated series of didactic instruction and supervised research training. This program will promote the understanding of stem cell and developmental biology, as applied to dentistry and future oral pathology. Dr. Fen Wang will mentor the principal investigator's scientific development. Dr. Wang is a recognized leader in the field of fibroblast growth factor (FGF) in developmental and cancer biology. He has trained numerous postdoctoral fellows and graduate students. To enhance the training, the program will enlist the expertise of Dr. D'Souza, Biomedical Science Chair, and Dr. Wright, Oral Pathology Chair. Research will focus on the roles of FGF in regulating the capability of self-renewal and differentiation in the odontogenic epithelial stem cells. The specific aims include: 1) characterize the cells and signaling in cervical loop region be affected in Fgfr2 tissue specific knockout mice during incisor development; 2) establish an odontogenic epithelial stem cell culture system; 3) determine the role of FGF/FGFR2/FRS21/MAPK signaling in self-renewal and differentiation of cervical loop odontogenic epithelial stem cells in 3D in vitro sphere culture. This will be the first establishment of odontogenic epithelial stem cell culture and detailed functional analysis of FGF using 3D in vitro sphere culture. These data will provide new insights into the role of FGF in regulating odontogenic epithelial stem cells and for future regeneration. The combination of the Institute of Biosciences and Technology and the biomedical sciences and oral pathology departments of Baylor College of Dentistry provides an ideal setting for training dentist-scientists by incorporating expertise from diverse resources into customized programs. Valuable knowledge can be gained from the research directed towards the development of regeneration application to aid in the prevention and treatment of odontogenic lesions and tumors in the future. Public Health Relevance: Stem cells derived from both epithelial and mesenchymal components are required for future regeneration of whole teeth. The key for reconstruction from defined cellular and molecular components and further elucidating the alterations in pathology depends on developing in vitro systems that accurately recapitulate the in vivo functions. Although Fibroblast Growth Factors (FGF) have been shown to play important roles in maintenance of the mouse incisor cervical loop region where stem cells are thought to reside, the defined mechanism of FGF signaling is not yet available for the odontogenic epithelial stem cells and surrounding microenvironment. Our project is aimed at defining the FGF signaling pathways for the odontogenic epithelial stem cells derived from mouse incisor cervical loops through an in vivo Fgfr2 tissue specific knockout mouse model and developing in vitro sphere culture model.